Abstract 455: Increased copy number of Septin 9 (SEPT9) in women with high grade endometrial adenocarcinoma(EMCA): Is there a potential link to paclitaxel resistance

Abstract

Abstract Septins are a unique family of GTPases that are important in the regulation of a variety of essential cellular functions. Specifically, SEPT9 has been demonstrated to be vital in normal development in a mouse model. When a full knockout is generated, the phenotype is embryonically lethal. SEPT9 has also been implicated in tumorigenesis and our group has identified SEPT9 as an oncogene which is amplified and overexpressed in breast cancer. We have demonstrated that in high grade breast carcinomas, the subtype with the worst clinical outcome, exhibit significant increases in SEPT9 copy number variation (CNV) when compared to other breast tumor grades. Therefore to explore a possible biomarker role of SEPT9 in other tumor types, we have investigated the CNV status of SEPT9 in EMCA using data from the publically available Cancer Genome Atlas (TCGA). Within the published dataset, 7.8% of patients have an increased CNV of the gene. The Kaplan-Meier survival curves between the 2 groups show a decreased overall survival in the EMCA patients who exhibit CNV (n=18) with a 5-year survival of 44% compared to 83% (p = 0.003) in the remaining EMCA patients without an alteration in CNV (n=214). Septins assemble into filaments that interact with the cytoskeleton. Published data on established cell lines with an overexpression of specific isoforms suggest an association between the overexpression and resistance to paclitaxel. Many high grade EMCA patients are treated with adjuvant paclitaxel-based regimens. We hypothesize that an increased CNV and overexpression of SEPT9 is associated with paclitaxel resistance on a molecular level and a worse clinical prognosis. To support our hypothesis, we will test established uterine papillary serous carcinoma cell lines (UPSC), an aggressive high grade EMCA, for CNV variation of SEPT9 and resistance to paclitaxel. In addition, tumor samples from patients with advanced stage (III-IV) UPSC will be investigated for an increased CNV of SEPT9. Citation Format: Jenna R. Zechmeister, Gary L. Goldberg, Cristina Montagna. Increased copy number of Septin 9 (SEPT9) in women with high grade endometrial adenocarcinoma(EMCA): Is there a potential link to paclitaxel resistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 455. doi:10.1158/1538-7445.AM2014-455